Amino acids perform multiple essential physiological roles in humans, and their importance in human health has been extensively studied in preclinical and clinical research. Enteropeptidase is a pivotal gut-localized enzyme that activates protein digestion events in mammals. SCO-792 is an orally available enteropeptidase inhibitor with first-in-class potential that inhibits gut amino acid intake into human circulation. In Phase 1 and 2 trials, SCO-792 demonstrated its safety and tolerability in humans.
Patients with inborn metabolic disorders affecting amino acid metabolism have clinically challenging conditions. Typical examples include phenylketonuria (PKU), maple syrup urine disease (MSUD), or homocystinuria (HCU). Dietary restriction of natural proteins, thereby reducing the intake of phenylalanine, branched-chain amino acids, and methionine, is a validated treatment for patients with PKU, MSUD, and HCU, respectively. However, adherence to lifelong dietary restrictions is a huge challenge for patients. Considering these factors, SCO-792-mediated inhibition of gut amino acid intake is a rational strategy for meeting unmet medical needs in treating amino acid-related disorders.
In a clinical trial, SCO-792 effectively decreased plasma amino acid levels derived from the diet or protein drinks, with an excellent safety profile in healthy individuals. This demonstrates a clinical proof-of-mechanism of SCO-792-mediated enteropeptidase inhibition for amino-acid-related diseases. Hence, SCO-792 is a potentially novel treatment solution for PKU, MSUD, HCU, and other amino acid metabolism disorders where dietary restriction of natural proteins is therapeutically effective.
Circulating amino acids also physiologically regulate the glomerular filtration rate, an indicator of human kidney function. Hence, a sustained intake of excess dietary protein likely impairs kidney function. Therefore, we suggest a novel strategy for inhibiting gut amino acid intake into the circulation to improve kidney function.
In preclinical studies, SCO-792 was highly effective in rodent models with nephrotic syndrome, a disease defined by severe proteinuria leading to hypoalbuminemia. In addition, in a Phase 2 proof-of-concept study, 12-week treatment with SCO-792 resulted in a clinically significant reduction in the urine albumin-to-creatinine ratio from baseline in patients with diabetic kidney disease (DKD). These suggest that SCO-792 may be a novel treatment option for nephrotic syndrome and DKD. Detailed information is available upon request.
SCOHIA is actively seeking partnerships worldwide for the development and commercialization of SCO-792 (Contact here for partnering).
Indication :
- Phenylketonuria (PKU)
- Maple syrup urine disease (MSUD)
- Homocystinuria (HCU)
- Diabetic kidney disease(DKD)
Clinical Trial Information
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SCOHIA initiates a phase 2 proof of concept study on an enteropeptidase inhibitor (SCO-792) for diabetic kidney disease
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SCOHIA initiates a phase 2 proof of concept study of an enteropeptidase inhibitor (SCO-792) in obese patients with type 2 diabetes mellitus
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Scientific Publication
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Publication of a clinical phase 2 study of SCO-792
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Publication of medicinal chemistry research on SCO-792, an enteropeptidase inhibitor
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Publication of a preclinical study: the enteropeptidase inhibitor SCO-792 is therapeutically effective for improving renal function in a nondiabetic rat model of chronic kidney disease
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Publication of a preclinical study: SCO-792, an enteropeptidase inhibitor, improves obesity via microbiota-driven mechanisms in mice
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Enteropeptidase inhibition improves kidney function in a rat model of diabetic kidney disease
・Diabetes, Obesity and Metabolism
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SCO-792, an enteropeptidase inhibitor, improves disease status of diabetes and obesity in mice.
・Diabetes, Obesity and Metabolism
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Discovery and characterization of a small-molecule enteropeptidase inhibitor, SCO-792.
・Pharmacology Research & Perspectives
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